Abstract / Summary
Abstract Background Vitamin B12 (B12) plays a crucial role in neurodevelopment, methylation pathways, mitochondrial function and its dysregulation has been implicated in Autism Spectrum Disorder (ASD). It is specifically required as a cofactor for the activity of two strictly B12 dependent enzymes: methionine synthase and methylmalonyl-CoA mutase thereby playing a crucial role in key metabolic pathways, including the conversion of homocysteine to methionine. Methods This observational study evaluated B12 levels in children from age 2 to 18 years diagnosed with ASD (according to DSM-5 criteria) and studied association of B12 levels with severity and behavioral features measured using Gilliam Autism Rating Scale (GARS) and social maturity using SQ scores. Results Our findings revealed that only 40% of children had optimum B12 levels. A substantial proportion 33% demonstrated elevated B12 levels, whereas 27% had B12 deficiency. In the profound ASD group 30.25% were B12 deficient, 31.9% had elevated B12 and 37.81% had optimum levels. Deficiency increased with age and elevated levels were common in younger age group. Deficiency was more prevalent among vegetarians than non-vegetarians, whereas elevated B12 levels were more frequently observed among non-vegetarians. Multivariable regression analysis also revealed that Age was significant predictors of both GARS and SQ scores, and Diet was a significant predictor of GARS whereas B12 was marginally associated with SQ after adjustment for covariates. Conclusion The heterogeneous distribution of B12 status across the ASD cohort suggests that B12 dysregulation may be more complex than a uniform deficiency state. The presence of elevated B12 levels may reflect impaired cellular utilization or altered cobalamin metabolism, highlighting the limitations of serum B12 as a sole indicator of functional cobalamin status. Since core symptoms and clinical severity were observed across all B12 categories, optimizing B12 levels alone may not produce predictable changes in ASD severity. Assessment of functional metabolic biomarkers and methylation related pathways is required in future studies. Optimizing B12 levels should be an adjunctive treatment strategy rather than a standalone.